Role of Minocycline in Acute Traumatic Spinal Cord Injury

Introduction: Spinal cord injury (SCI) from mechanical trauma triggers inflammatory and degenerative pathways leading to demyelination, axonal injury, and apoptosis. Neuroprotective agents like minocycline may limit post-traumatic damage to enhance clinical outcome. This review evaluates the neuroprotective potential of minocycline in SCI functional recovery and rehabilitation.

Methods: A systematic review, following PRISMA guidelines, identified 280 articles through PubMed and Embase from January 2000 to July 2024. Inclusion criteria involved human or animal trials assessing minocycline administration post-acute SCI with functional or molecular outcomes.

Results: Among 25 studies included in the analysis, 3 were human trials with use of intravenous minocycline. In 22 animal studies, minocycline was administered intraperitoneally (12 studies), orally (3), intravenously (2), subdurally (1), or as intraparenchymal nanoparticles (1). Human doses ranged from 200–400 mg immediately post-injury for up to 7 days; animal doses ranged from 1–180 mg/kg for up to 2 weeks. Higher doses were associated with improved treatment outcomes. Three studies administered minocycline prophylactically, 12 hours to 30 minutes prior to SCI. While minocycline treatment showed improvements for functional outcomes in cervical injury, 2 studies with CSF biomarker analysis showed decreases in substrates that correlate with more severe injury suggestive of potential targets and role for minocycline therapeutically. Animal studies indicated significant improvements in functional outcomes, lesion size, white matter preservation, reduction in reactive astroglia and protection of oligodendrocytes after minocycline treatment. Further, a decrease in inflammatory cytokines (IL-6, IL-1ß, and TNF-alpha), and suppressed activation of microglia, recruitment of macrophages, reduced apoptosis and improved antioxidant status were observed.

Conclusion : Minocycline as a neuroprotective therapeutic in acute SCI may modulate secondary degenerative responses with potential for clinical benefit. While its safety profile is better understood in animal trials, further human trials are needed to assess clinical benefits and safety profile of minocycline.